📬 GYN Oncology Intelligence Digest — Week 2026-W35

OPAL cohort C closed for futility as neoadjuvant niraparib reached 31.6% ORR versus 70.6% with platinum-taxane in HRd advanced ovarian cancer; TEDOVA reported HR 0.53 for OSE2101 plus pembrolizumab maintenance, PYNNACLE reported a 44.4% ORR with rezatapopt in TP53 Y220C-mutated ovarian cancer, and the FDA granted fast track to sapanisertib/serabelisib plus paclitaxel in PI3K/AKT/mTOR-altered endometrial cancer.

⚡ TL;DR

📄 Publications

Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination-deficient stage III/IV ovarian cancer: Findings from cohort C of the OPAL phase 2 trial. — Of 36 patients randomized, 19 received niraparib and 17 platinum-taxane

🐦 Twitter / 🦋 Bluesky

Genome-wide in vivo CRISPR screens name P2RY8 and GNAS as brakes on human T cells in solid tumors, including uterine sarcoma models — The work is described as the first genome-wide in vivo screens for genetic modifications to enhance human T cell therapies for solid tumors, published in Nature
Update: ETOP IBCSG ADC position statement circulates again as the same week brings new B7-H4 and cervical ADC target data — The position paper summarizes expert recommendations for advancing antibody-drug conjugate research and clinical use across solid tumors, with ADCs increasingly standard in ovarian and cervical cancers
PYNNACLE: rezatapopt produces a 44.4% ORR in TP53 Y220C-mutated advanced ovarian cancer as enrollment completes — In the phase II PYNNACLE trial, rezatapopt showed antitumor activity in heavily pretreated TP53 Y220C-mutated advanced ovarian cancer with a 44.4% ORR and 8.2 months median duration of response
TEDOVA: OSE2101 plus pembrolizumab maintenance cuts progression risk versus best supportive care in platinum-sensitive ovarian cancer — OSE2101 plus pembrolizumab beat best supportive care as maintenance in platinum-sensitive ovarian cancer with HR 0.53, P < .001, a nearly 50% reduction in risk of progression

Full details below ↓

📄 What's Being Published

Manuscripts:

Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination-deficient stage III/IV ovarian cancer: Findings from cohort C of the OPAL phase 2 trial. — Westin Shannon N et al., Gynecol Oncol

Of 36 patients randomized, 19 received niraparib and 17 platinum-taxane; the pre-IDS unconfirmed ORR was 31.6% with niraparib versus 70.6% with platinum-taxane, a difference of -39.0% (80% CI -56.8% to -17.7%) favoring platinum-taxane, and the trial was closed early for futility. Grade ≥3 adverse-event rates during the neoadjuvant period were 42% with niraparib and 59% with platinum-taxane.

Clinical bottom line: Neoadjuvant niraparib should not replace platinum-taxane chemotherapy before interval debulking in HRd stage III/IV ovarian cancer — response rates were less than half those of chemotherapy and the cohort was stopped for futility.

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🗂 Every paper considered this week, including the ones that didn’t make it →

🗣️ What People Were Discussing This Week

How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).

Genome-wide in vivo CRISPR screens name P2RY8 and GNAS as brakes on human T cells in solid tumors, including uterine sarcoma models

Described as the first genome-wide in vivo screens for genetic modifications to enhance human T cell therapies for solid tumors and published in Nature, the work identified two suppressive nodes: P2RY8, which appeared to make it harder for T cells to enter tumors, and GNAS, which helped transmit several of the suppressive signals tumors use to shut T cells down. In one melanoma model, all 6 mice treated with GNAS-edited CAR T cells achieved durable tumor clearance, and the approach also improved tumor control across other preclinical models including uterine sarcoma. The central debate is whether engineered T-cell products for gynecologic tumors should be edited at multiple suppressive nodes such as P2RY8 and GNAS rather than carrying a single added receptor.

Discussed by: @EladSharonMD, @EladSharonMD

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Update: ETOP IBCSG ADC position statement circulates again as the same week brings new B7-H4 and cervical ADC target data

The ETOP IBCSG position paper summarizes expert recommendations for advancing antibody-drug conjugate research and clinical use across solid tumors — with ADCs increasingly standard in ovarian and cervical cancers — and lists careful selection of trials for phase III, predictive biomarkers, construct and target optimization, and biomarker heterogeneity as stated priorities. Alongside the position statement, a multi-layered screening strategy identifies MSLN, TROP-2, and LIV-1 as potential precision therapy targets in cervical cancer, and mocertatug rezetecan demonstrated robust response rates and a manageable safety profile as monotherapy in the phase 1 BEHOLD-1 study in patients with advanced gynecologic malignancies. The field is weighing which predictive biomarker to require before advancing a B7-H4 or MSLN construct into phase III.

Discussed by: @OncoAlert, @Inside_PM, @OncLive, @onclive.bsky.social

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PYNNACLE: rezatapopt produces a 44.4% ORR in TP53 Y220C-mutated advanced ovarian cancer as enrollment completes

In the phase II PYNNACLE trial, rezatapopt showed antitumor activity in heavily pretreated patients with TP53 Y220C-mutated advanced ovarian cancer, with a 44.4% ORR and 8.2 months median duration of response. Phase 2 enrollment has since completed, with PMV targeting a 2027 ovarian cancer NDA. Clinicians are now debating whether a single TP53 hotspot such as Y220C is worth routine reporting in recurrent ovarian cancer sequencing panels.

Discussed by: @ASCOPost, @BNTBriefing

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TEDOVA: OSE2101 plus pembrolizumab maintenance cuts progression risk versus best supportive care in platinum-sensitive ovarian cancer

The TEDOVA trial reported that OSE2101 plus pembrolizumab beat best supportive care as maintenance in platinum-sensitive ovarian cancer, with HR 0.53 (P < .001) — a nearly 50% reduction in risk of progression. Sequencing decisions at relapse are being framed around secondary cytoreduction candidacy, platinum re-treatment strategy, and maintenance selection by response, prior therapy, and biomarkers. The open question is whether a vaccine-plus-checkpoint maintenance strategy competes with PARP inhibitor maintenance in platinum-sensitive relapse, or whether it is best positioned for the PARP-exhausted patient.

Discussed by: @OncLive, @MedwatchKate

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🔥 Top Ranked Tweets

Dr Rupam Manna MD @DrRupamOncology

Tisotumab vedotin is a tissue-factor ADC with MMAE for post-chemotherapy recurrent/metastatic cervical cancer. innovaTV 301: OS HR 0.70. Mandatory eye care: examination, steroid + vasoconstrictor drops, cold packs and lubricants. #CervicalCancer #ADC https://t.co/DxzRMyaYLf

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